Kennedy's (SBMA) neuron disease: The availability of the complete AR sequence quickly led to finding that SBMA patients have mutated AR sequences with longer poly glutamine (polyQ) regions thus permitted this mutated AR to interact with other proteins (coregulators), forming a nuclear aggregation that interrupted neuronal functioning. In 1996, Dr. Chang's team isolated the first AR coregulator (PNAS, 1996), and from there, they screened the first anti-AR compound (ASC-J9) that interrupted the interaction between the AR coregulator(s) and the AR leading to AR protein degradation. Testing in mice proved that ASC-J9 could improve SBMA disease symptoms markedly by decreasing the AR-polyQ aggregations. Moreover, SBMA mice treated with ASC-J9 retained normal sexual function and fertility (Yang et al, and Chang, Nature Medicine, 2007). This continual effort from cloning AR, to isolation and characterizing of AR coregulators, to finding a compound to provide better treatment for SBMA, truly represents an idea of from the bench to the bedside.

Prostate Cancer: Androgen deprivation therapy (ADT) with medical/surgical castration has remained as the standard treatment of advanced prostate cancer for the past 70 years. Yet, most tumors eventually recur and patients die. Cloning the AR (Chang, et al, Science, 1988) and generation AR antibodies (Chang, et al, Endocrinology, 1989) allowed clinicians to monitor the AR status of processing prostate tumors, finding that classic ADT failed to eliminate the prostate AR. Classic ADT failed to eliminate the prostate AR and tumor recur, subsequent findings suggest the reason can be (a) AR functions differentially in different prostate cells: suppressor in epitheial basal cells; survivor in epithelial luminal cells and proliferators in stromal cells (Niu et al and Chang PNAS 2008) Since classic ADT target systemic androgen and not specific to prostate cells with AR positive roles, it should fail. (b) In addition to classic androgens (T and DIH), prostate AR can be also activated by non-androgens, such as estrogens (Yeh, et al and Chang, PNAS, 1998), the antiandrogen flutamide (Yeh, Miyamoto and Chang, Lancet, 1997), and delta 5-androstenedione (Miyamoto, et al and Chang, PNAS, 1998). These findings led to investigating new therapeutic approaches which targeted the AR (and not androgens, as current ADT standardly does.). The results from early animal tests which targeted the AR by either ASC-J9 or AR-siRNA showed the suppression of tumor progression of prostate cancers. In summary, from cloning AR (Chang et al. Science 1988) to develop ASC-J9 to target AR in selective cells (Yang et al and Chang, Nat. Med. 2007) the 20 years continue AR studies in Dr. Chang¹s lab not only advance our understanding the AR function in prostate, may also lead to develop better therapeutic approaches to battle prostate cancer

Female AR-related diseases: The successful generation of the first cell-specific knockout AR mouse (Yeh, et al and Chang, PNAS, 2002) allowed Dr. Chang's Lab to develop the first female animal without a functional AR. Later on, using these mice, Dr. Chang's Lab found that the AR plays an important role in female breast development and breast cancer progression (Yeh et al, and Chang, JEM, 2003) as well as fertility and folliculogenesis (Hu et al, and Chang, PNAS, 2004). These findings opened a new field for studying the AR's role(s) in female health and diseases.

The discovery of TR2/TR4 orphan nuclear receptors: TR2 represents the first identified orphan receptor (without counting RXR) in the nuclear receptor superfamily (Chang et al, BBRC, 1988). The natural ligand(s) of these "receptors" remain unidentified. Over 90% of published papers related to TR2/TR4 have come from Dr. Chang's Lab, TR2/TR4 are master regulators of many bio-physiological functions. Knockout of TR2 and/or TR4 results in accelerated aging, abnormal metabolism and insulin sensitivity, and fertility and neurological dysfunctions (Collins et al and Chang, PNAS, 2004; Chen et al and Chang, MCB, 2005). Several compounds that can modulate kinase activity can modulate TR2/TR4 transactivation. Continued research on TR2/TR4 in the future may provide a new target for drug development to treat or prevent many "disease" processes, such as aging, diabetes, and neuro-dysfunctions.

In summary, Dr. Chang's Lab has been responsible for many key discoveries and developing several essential reagents for studying AR. Today, more than 700 laboratories are utilizing AR-related reagents (such as AR-cDNA, AR-antibodies, AR-siRNA, AR-5'-promoter reporter, AR-coregulators, AR knockout mice, and the anti-AR ASC-J9) generated in Dr. Chang's Lab. The whole AR field has received far-reaching benefits from the discoveries made by Dr. Chang and his co-workers.